Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, USA.

Abstract

Organocatalysts derived from diethylenetriamine effect the rapid isomerization of non-native protein disulfide bonds to native ones. These catalysts contain a pendant hydrophobic moiety to encourage interaction with the non-native state, and two thiol groups with low pKa values that form a disulfide bond with a high E°' value.

Catalysis of disulfide-bond isomerization by PDI and PDI mimics 1–7. (A) Graph of the time-course for the isomerization of sRNase A to give native RNase A. All assays were performed in triplicate at 30 °C in 50 mM Tris–HCl buffer, pH 7.6, containing GSH (1.0 mM), GSSG (0.2 mM), and PDI or dithiol 1–7 (1.0 mM). (B) Graph of the yield of native RNase A achieved by PDI mimics 2–7 after 5 h as a function of the logP value of its side chain ().